The study is designed as a Phase II, prospective, non randomized, open-label, single arm, multicenter trial, in which patients with locally advanced or metastatic ACC not amenable to complete surgical resection and progressing to cytotoxic chemotherapy will receive Sorafenib plus metronomic chemotherapy as treatment.The aim of this phase II trial is to evaluate the clinical benefit and toxicity of the combination of Sorafenib plus metronomic chemotherapy in patients with locally advanced or metastatic ACC who progressed after first or second line chemotherapy.

The study is designed as a Phase II, prospective, non randomized, open-label, single arm, multicenter trial, in which patients with locally advanced or metastatic ACC not amenable to complete surgical resection.

STUDY OBJECTIVES

The aim of this phase II trial is to evaluate the clinical benefit and toxicity of the combination of Sorafenib plus metronomic chemotherapy in patients with locally advanced or metastatic ACC who progressed after first or second line chemotherapy.

Primary objective

To assess the clinical benefit as measured by a non progressing rate after 4 months of the combination of Sorafenib plus weekly Paclitaxel in patients with locally advanced or metastatic ACC who progressed after first or second line chemotherapy.

Secondary objectives

Assessment of Objective (Complete and Partial) Response Rates

Assessment of Duration of Response

Assessment of Hormonal Response

Assessment of Progression-Free Survival

Assessment of Overall Survival

Assessment of the relationship between specific "biomarkers" and cancer- and treatment-related outcomes

Assessment of Quality of Life by EORTC QLQ-C30

Assessment of Toxicity

ENDPOINTS

The first disease assessment will be performed after 8-weeks, subsequent assessments will be performed every 12 weeks until end of the study.

Primary endpoint

Progression-Free Survival rate ≥ 40% after 4 months

Secondary endpoints

Response rate evaluation will be performed according to the RECIST criteria. The same methods of measurement and the same technique should be used to characterize each identified and reported lesion at baseline and during study.

PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.]

Serum creatinine < 1.5 x upper limit of normal

Effective contraception in pre-menopausal female and male patients

Patient´s written informed consent

Ability to comply with the protocol procedures

Exclusion criteria:

History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least three years.

History of HIV infection or chronic hepatitis B or C (This criteria should be modified to allow Hepatitis B or C in protocols looking at HCC patient population)

Active clinically serious infections (> grade 2 NCI-CTC version 3.0)

Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)

Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study]

Current treatment with another investigational drug

Any other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00786110

Locations

Italy

Department of Clinical and Biological Sciences, University of Turin

Orbassano, Italy

Azienda Ospedaliera di Padova

Padova, Italy

Azienda Ospedaliera Università di Palermo

Palermo, Italy

Policlinico Universitario Campus Biomedico- Roma

Roma, Italy

Ist. Clin.Humanitas

Rozzano, Italy

Sponsors and Collaborators

University of Turin, Italy

Investigators

Study Chair:

Alfredo Berruti MD

Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, Italy